This overexpression was lost, however, in some advanced cases: 89% and 81% of TNM (tumour, node, metastases) stages 0-II showed Nm23-H1 and -H2 overexpression, respectively, which significantly differed from 47% and 38% of stage III-IV tumours.
Allelic imbalance at NME1 in microdissected primary and metastatic human colorectal carcinomas is frequent but not associated with metastasis to lymph nodes or liver.
Expression of nm23-H1 (NME1), a known metastasis-suppressor gene in this breast cancer cell line, did not correlate with metastasis suppression in the microcell hybrids.
There was an increased expression of ets-2 in 30% of RA samples and an up to 30-fold decreased expression of the potential metastasis suppressor gene nm23-H1 in 90% of RA tissues, compared with control tissues.
The data identify the first structural motifs of nm23-H1 that influence its metastasis suppressive effect and suggest complex biochemical associations or activities in the Nm23 suppressive pathway.
There was a strong inverse correlation between the levels of nm23 mRNA expression and nm23 antigen expression and the development of metastases of all seven human uveal melanomas and both murine skin melanomas transplanted intracamerally.
The expression of nm23, a putative metastasis-suppressor gene product, was assessed immunohistochemically in malignant and benign ovarian neoplasms, considering histology of tumors and clinical advancement of disease.
There was no inverse correlation between the nm23 protein and melanoma metastasis which suggested that the nm23 protein does not appear to be lost during melanoma metastasis.
However, this trend was not maintained in cancer cells from tumors that metastasized to axillary lymph nodes and in metastatic cells; in these 2 situations the NM23.H1 mRNA content varied without any relationship to the proliferative rate of the cells.
We have analyzed expression of nm23 polypeptide in acquired melanocytic nevi (n = 19), dysplastic nevi (n = 19), malignant melanomas (n = 22) and metastases of malignant melanomas (n = 47) in situ.
However, the possibility of nm23 loss occurring in association with metastasiscannot beruled out in some more aggressive sarcomas, as was demonstrated for six patients with low-scoring, unclassified and synovial sarcomas that had metastasized.
This nm23 positivity was inversely associated with scleral invasion level (P = 0.001) and largest tumour diameter (P = 0.02), which represent the two most significant prognostic factors for metastasis.
Since nm23 gene family members have been proposed to play a role in cellular differentiation, as well as in metastasis suppression, we investigated whether and how DR-nm23, a recently identified third member of the human nm23 gene family, might be involved in neuroblastoma differentiation.
When studying Bgl II RFLPs, allelic losses of the nm23 gene were found in 3/12 (25%) informative tumors, and all 3 had lymph node and/or distant metastases.